The biology of hunger

The biological mechanisms behind hunger, appetite, and satiety are mysterious. What processes cause us to feel hunger and then tell us when to stop eating? Why are we attracted to particular foods more than others? What are the biological roots of eating disorders like binge eating and anorexia?

For Nilay Yapici, Neurobiology and Behavior, the answers lie in our brains. “I’ve always been fascinated by how our brains control our behaviors,” she says. “I want to understand how genes regulate our brain functions, which then control our behaviors, especially our daily life decisions like eating.”

Identifying Food Intake Neurons

Yapici explores how the food intake circuits in the brain are regulated in different behavioral states. Her lab seeks to identify neurons that mediate food intake decisions and trace their activity during various behaviors, such as foraging or resting.

Yapici began her research career focusing on Drosophila melanogaster, the fruit fly. She wanted to explore the genetics behind behavior, and she was drawn to drosophila because it has a smaller brain with 1000-fold fewer neurons than the mouse brain, yet approximately 80 percent of the protein-coding genes in drosophila are the same as in other species, such as mice and humans.

Early on, the Yapici lab identified excitatory interneurons, which they called Ingestion Neurons 1 (IN1), in the taste-processing center of the drosophila brain. “These neurons change activity when the fly is hungry,” Yapici says. “They have a higher firing rate when the fly is actively eating. We think the activity of these neurons is controlling the persistence of food intake.”

A Gut-Brain Positive Feedback Loop?

In their quest to understand the role of IN1 in food intake in drosophila, the researchers began to look at the interaction between the fly’s brain and its gut. “We have preliminary evidence that the duration of food intake may be regulated by information coming from the gut,” Yapici says. “It’s like a positive feedback loop. If the fly is eating something good, neurons in the gut seem to be activated and send impulses to the IN1 neurons in the brain. We think that’s why the IN1 neurons are persistently active while the fly is eating. It’s almost like the gut is telling the brain, ‘This is good. Keep on eating.’”

Recent research from other labs appears to show that these gut-brain neurons also exist in mice, Yapici explains. “This is encouraging to me because it seems similar mechanisms exist in both drosophila and mice, which makes the fly model more promising in terms of using it to understand the neural circuits that regulate food intake in the brain,” she says.

“The duration of food intake may be regulated by information coming from the gut. It’s like a positive feedback loop ... It’s almost like the gut is telling the brain, ‘This is good. Keep on eating.’”

Yapici and her lab are planning to use the fly model to identify specific genes of interest, and then to take those findings and apply them to more complicated mouse models. “We’ll be going back and forth between the two models, and learning from both at the same time,” she says.

Imaging Deep Regions of the Brain

To peer into the deep regions of the mouse brain, Yapici has an ongoing collaboration with Chris Xu, Applied and Engineering Physics. Xu is the lead principle investigator (PI) and Yapici is a co-PI for the Cornell Neurotechnology Hub, which is dedicated to developing new brain-imaging technologies and making them known to the neuroscience community. Yapici and Xu worked together to develop a method to image deep regions of the living fly brain without surgery. Recently they extended that work further, seeking to create new methods to image the mouse brain stem.

“We are trying to image really deep regions in the brain,” Yapici says. “These regions are very important for taste processing and also probably for communicating with the gut. In addition, they contain other neural circuits that regulate physiological functions, like sleep and motor behaviors. No one can access them in behaving animals because of the technical difficulties of imaging them, but if we can develop this new imaging method using three-photon microscopy, there will be a lot of applications for its use. I’m very excited about that.”

What Is the Volume of One Fly Gulp?

Although she is not a trained engineer, Yapici is no stranger to inventing new tools to address scientific questions in the lab. Some years ago, she developed an ingenious one, called Expresso, to measure food intake for individual flies. Expresso is made up of many tiny glass capillaries that contain an exact measure of liquid food and a sensor that can detect the meniscus in the glass capillaries. The researchers put one fly in a chamber with one capillary to feed from.

“We can determine the volume of each gulp a fly takes,” Yapici says. “At the same time, we can track the flies. So, we know how much a fly eats and then what they do before and after they eat. Do they hang out in a corner? Do they stay close to the food? Do they forage for other food? It’s a very quantitative way of measuring fly feeding and foraging.”

A Passion for Understanding the Brain

In college, Yapici considered studying engineering but was always fascinated more by biology. “I even almost became a neurosurgeon,” she says. “But my passion was for understanding the brain rather than curing it. The research I do is basic science, but I like working on a question that has some kind of applied goal in the future. I don’t think I’m going to develop a therapy for an eating disorder, but I might actually identify a mechanism that can be used by someone else to develop a therapy. That’s the way science is. It’s a group effort. You need a lot of complementary scientific knowledge and expertise to reach a final goal.”